1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEMocetinostatCat. No.: HY-12164CAS No.: 726169-73-9Synonyms: MGCD0103分式: CHNO分量: 396.44作靶點: HDAC; Autophagy作通路: Cell Cycle/DNA Damage; Epigenetics; Autophagy儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解

2、性數(shù)據(jù)體外實驗 DMSO : 50 mg/mL (126.12 mM; Need ultrasonic)H2O : 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (6.31 mM); Clear solution1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEBIOLOGICAL ACTIVITY物活性 Mocetinostat (MGCD0103)種有效，可服和同種型選擇性的 HDAC (Class I/IV) 抑制劑，抑制HDAC1，HDAC2，HDAC3 和 HDAC11 的

3、IC50分別為0.15，0.29，1.66 和 0.59 M。 Mocetinostat對HDAC4，HDAC5，HDAC6，HDAC7或HDAC8沒有抑制作。IC50 & Target HDAC1 HDAC2 HDAC11 HDAC30.15 M (IC50) 0.29 M (IC50) 0.59 M (IC50) 1.66 M (IC50)體外研究 Mocetinostat is a potent, orally active and isotype-selective HDAC (Class I/IV) inhibitor with IC50s of 0.15,0.29, 1.66 an

4、d 0.59 M for HDAC1, HDAC2, HDAC3 and HDAC11, respectively. Mocetinostat shows noinhibition on HDAC4, HDAC5, HDAC6, HDAC7, or HDAC8. Mocetinostat (MGCD0103) exhibits potent andselective antiproliferative activities against a broad spectrum of human cancer cell lines in vitro, and HDACinhibitory activ

5、ity is required for these effects. In all cell lines tested, Mocetinostat (MGCD0103) partiallyinhibits cellular HDAC enzyme activity although the maximal inhibition of activity varies among cell lines from75% to 85% of total activity. The IC50 of Mocetinostat in intact cancer cells is independent of

6、 tissue origin. InA549 cells, MGCD0103 shows dose-dependent inhibition of HDAC activity in whole cells. At highconcentrations in A549 cells, Mocetinostat inhibits a maximum of 80% of total activity. In HCT116 cells,Mocetinostat induces a significant S-phase depletion and both G1 and G2-M accumulatio

7、n 1.體內(nèi)研究 Mocetinostat (MGCD0103) significantly inhibits growth of human tumor xenografts in nude mice in a dose-dependent manner and the antitumor activity correlated with induction of histone acetylation in tumors. Thep.o. administration of Mocetinostat (MGCD0103) (2HBr salt) significantly reduces

8、growth of implantedadvanced A549 tumors in nude mice in a dose-dependent manner after 13 days of daily administration.Mocetinostat (170 mg/kg for 2HBr salt, corresponding to 120 mg/kg of free base) significantly blocks growthof tumors compared with vehicle treatment alone (P 1.PROTOCOLKinase Assay 1

9、 The deacetylase enzyme assay is based on a homogeneous fluorescence release assay. Purifiedrecombinant HDAC enzymes are incubated with Mocetinostat (MGCD0103) diluted in various concentrationsfor 10 min in assay buffer 25 mM HEPES (pH 8.0), 137 mM NaCl, 1 mM MgCl2, 2.7 mM KCl at roomtemperature. Th

10、e substrate Boc-Lys(-Ac)-AMC (Bachem) is added to the reaction for further incubation at37C. The concentration of the substrate and the incubation time varies for different isotypes of HDACenzymes. A 20-min trypsin incubation at room temperature allows the release of the fluorophore from thedeacetyl

11、ated substrate. The fluorescent signal is detected by fluorometer at excitation of 360 nm, emission of470 nm, and cutoff at 435 nm. The IC50 values of the compounds are determined by analyzing dose-response inhibition curves 1.MCE has not independently confirmed the accuracy of these methods. They a

12、re for reference only.Cell Assay 1 Cells in 96-well plates are incubated with Mocetinostat at various concentrations for 72 h at 37C in 5% CO2.MTT is added at a final concentration of 0.5 mg/mL and incubated with the cells for 4 h before an equalvolume of solubilization buffer 50% N,N-dimethylformam

13、ide, 20% SDS (pH 4.7) is added. After overnightincubation, solubilized dye is quantified by reading at 570 nm using a reference at 630 nm. Absorbance2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEvalues are converted to cell numbers according to a standard growth curve of the relevant cell line. T

14、heconcentration which reduces cell numbers to 50% relative to DMSO-treated cells is determined as MTT IC501.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice 1Administration 12 Female CD-1 nude mice, ages 8 to 10 wk are used. Tumor fragments (

15、30 mg), which have been seriallypassaged thrice in vivo in minimal, are implanted s.c. through a small surgical incision on the flank of themice while under general anesthesia. Mocetinostat is dissolved in vehicle (PBS acidified with 0.1 N HCl orPEG400/0.2 N HCl saline, 40:60) and dosed p.o. as solu

16、tions daily. Tumor volumes and body weight aremonitored thrice weekly for at least 2 wk. Each experimental group containe six to eight animals. Forpharmacokinetic study, blood is collected from animals at various time points, and plasma samples areanalyzed using an Agilent 1100 HPLC system coupled w

17、ith an MDS Sciex API2000 triple quadrupole massspectrometer.Rats 2Forty rats (22020 g) are randomly divided into four different dosages of Mocetinostat groups (Low group,Medium group, High group, and control group with 10 rats in each group). Mocetinostat is dissolved in cornoil as suspension at thr

18、ee different concentrations (20, 40, and 80 mg/mL). Three different Mocetinostatgroups (Low group, Medium group, and High group) are respectively given Mocetinostat 20, 40, and 80mg/kg one time by intragastric administration at every morning and last for 7 days. Control group are givensaline by same

19、 administration method. At 8 days morning, six probe drugs, Bupropion, Phenacetin,Tolbutamide, Metoprolol, Testosterone, and Omeprazole, are mixed in corn oil and given to the rats of threeMocetinostat groups and control group by intragastric administration at a single dosage of 10 mg/kg forBupropion, Phenacetin, Metoprolol, Testosterone, and Omeprazole and 1 mg/kg for Tolbutamide.MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻 Proc Natl Acad Sci U S A. 2019 Feb 19;116(8):2961-